HIV-1 has been known to infect a variety of non-lymphoid cell lines, where the mode of entry has been postulated to involve an additional or an independent receptor or a second messenger-like molecule. In order to investigate the mechanism of viral replication in these cells we first tested the infectability of these cell lines with the HIV-IIIB strain and HIV-2 ROD strain. The cell lines we tested were SKNSH, SKNMC (neuroblastoma cell lines), HIB-14 (derived from an astrocytoma), A-204 and RD114 (rhabdomyosarcoma). All of them were infectable with both HIV-1 and HIV-2. We are studying the kinetics of replication of the 2 viruses in these cell lines, the pattern of gene expression (i.e., comparison with that observed in lymphoid cells. Studies are also in progress to examine the infectability of other possible target cells such as mammary epithelial cells which may have implications for virus transmission by the maternal- fetal route. These studies would also enable us to better define the cell or tissue specific factors that permit the course of the infection.